This
is another post in a series detailing the selection of antidepressant
medication. Use the “Antidepressants” link in the
“Categories”
part of the sidebar to find the other posts in the series.

In this post, I am sort of assuming that the reader has read the
previous posts, or has an adequate fund of general knowledge on the
subject.

Bupropion
is not a member of a family. Most antidepressants can be
placed
in a family of drugs that share similar properties, but there is no
other drug like it, as of the time of this writing. It is
sometimes referred to as a norepinephrine-dopamine
reuptake inhibitor
(NDRI) but in my mind it does not make sense to give it a class name if
there is only one member of the class. (It is rumored that an active
metabolite, hydroxybupropion, may be marketed eventually, but
development is on hold at the present time.)

Bupropion, then, is unique. For that reason, it deserves
particular attention…

The
most significant thing about bupropion is that it has no effect on
serotonin. Therefore, many the adverse effects associated
with SSRIs are absent. In particular, bupropion has a very
low likelihood of causing sexual dysfunction. That is a pretty big
plus, and that fact alone probably accounts for the popularity of the
drug.

Also, there is little if any risk of weight gain or sedation, and very
little risk of dry mouth or constipation. These properties
make bupropion very different from the tricyclic antidepressants.

There are some relative disadvantages, naturally. Bupropion
has no antiobsessive effect, and for most people it has little
beneficial effect on any kind of anxiety. Unlike SSRIs, TCAs,
and MAOIs, it is not good for panic disorder. It is not
effective for social phobia. Some people seem to get some
benefit for generalized anxiety. In general, though,
bupropion is not helpful for anxiety disorders for most people.

The most commonly seen troublesome adverse effects are insomnia and
tremor; some people feel restless or jittery from it.

There is virtually no abuse potential. There are sporadic
reports of people crushing the tablets and snorting the powder, but for
the vast majority of people this does nothing that is desirable.

The main risk associated with bupropion is that it lowers the seizure
threshold. That is, it increases the probability of seizures.
At normal doses this effect is not clinically significant, so
long two conditions are met. The person should not have any
predisposition to having seizures, and the person should not be taking
any other substance that would either lower the seizure threshold
significantly, or delay the metabolism of bupropion significantly.

The metabolism is a bit complex, but by and large the clinically
significant interactions occur with the cytochrome P450 enzyme, CYP2B6.
This is a known effect of many
antiretroviral drugs, and some
antidepressants: sertraline, paroxetine, norfluoxetine (the
active metabolite of fluoxetine), and fluvoxamine.

In actual practice, it is common for bupropion to be administered along
with some of the drugs that inhibit CYP2B6, but it is a good idea to be
cautious with these drug combinations. The modern
antidepressants
that are least likely to cause this interaction are citalopram,
escitalopram, and venlafaxine.

Clinical conditions that present an elevated risk from the lowering of
seizure threshold include epilepsy, traumatic brain injury, and eating
disorders.

Bupropion is sometimes used to treat conditions other than depression.
The most established such use is the treatment of nicotine
dependence.
For reasons that are clear only to FDA bureaucrats, bupropion
is
packaged and labeled separately for this purpose, as Zyban.
Zyban
has exactly the same active ingredient as Wellbutrin and all generic
forms of bupropion.

Some of the neuroscience fans who might be reading this might wonder
why a drug that inhibits reuptake of dopamine and norepinephrine would
have anything to do with nicotine dependence. The answer is
that
bupropion also acts as an antagonist for certain nicotine
receptors (PDF link).

Bupropion is also being studied in combination with naltrexone for the
treatment of obesity. Contrave
(TM) is a combination for this purpose, currently in Phase II trials by
Orexigen Therapeutics. Incidentally, IntelGenx Technologies
is
developing a combination of bupropion and mecamylamine,QuitPak,
as a sort of supercharged Zyban for smoking cessation.

So, enough of the background. What does this all mean when it
comes to the issue of selection of an antidepressant?

Bupropion
is particularly good for people who have, or wish to avoid, sexual
dysfunction,weight gain, or somnolence caused by other antidepressants.

Bupropion could be good choice for people who want to quit smoking,
have ADHD, or who have a problem with dependence on stimulants.
Personally, I have not been impressed by its effect on ADHD.
However, everyone is different, and if there is a chance to
use one drug (rather than two) for two conditions, it is good to try to
do so.

Bupropion is
not particularly good for people who want to treat both anxiety and
depression with one medication. It should be used with
caution,
if at all, in people who have risk factors for seizures, or who are
unavoidably taking a drug that interacts negatively with bupropion.

There’s good evidence for bupropion augmentation in the level 2 reports for Star*D trials.

Do you see that bupropion is one of the most misused antidepressants prescribed by well-meaning non-psychiatrists? Family docs (and even OB folk) seemed strangely partial to it (expressedly for lack of sexual side effects) as monotherapy, despite presence of comorbid anxiety for which, as you point out, we don’t have positive evidence.

I don’t have access to data that would tell us if prescriptions for combinations of SSRIs and Wellbutrin are increasing, but I can say that I have the subjective impression that it is so.

It isn’t possible to say if it is good, in general. You would have to look at each instance and decide in each case whether the combination makes sense.

I can make a couple of general comments, though. I can say that it is common for persons with depression to be treated inadequately; that is, they are given treatments that result in improvement (response), without attaining remission. If the use of these combinations is an indication that the physicians are making more of an effort to treat until remission in achieved, then it is good. Or, if it is a sign that the physicians are sensitive to the patient’s reports of adverse effects, then it is good.

On the other hand, if there are cases of polypharmacy resulting from uninformed prescribing, it is bad. I would be particularly concerned about the possibility that some of these prescriptions could be written without adequate regard for pharmacokinetic drug interactions.

If Wellbutrin is being increasingly prescribed, either on its own or as augmentation, perhaps physicians are preferring it in cases where they are treating chain-smoking clinical depressives who want or need to quit smoking. Just a thought.

My husband was given Wellbutrin to quit smoking and somehow it made him very irritable.He definitely experienced sexual dysfunction while on it, as well as difficulty urinating. My father, who’s stupidly and scarily aggressive if he’s not on antidepressants, said he had a similar experience when his doc tried Wellbutrin on him. I was on Wellbutrin for like 3 years and I never had adverse effects. I was switched like a year ago to another drug due to a convulsive syncope (due to lowered sugar levels according to my neurologist), and rather miss the non-drowsiness of Wellbutrin.

If Wellbutrin is being increasingly prescribed, either on its own or as augmentation, perhaps physicians are preferring it in cases where they are treating chain-smoking clinical depressives who want or need to quit smoking. Just a thought.

Very nice. Thanks you. Family docs (and even OB folk) seemed strangely partial to it (expressedly for lack of sexual side effects) as monotherapy, despite presence of comorbid anxiety for which, as you point out, we don’t have positive evidence.

But you can create a couple of general comments. I treat the depression that poor people are common, so this treatment is given why this improvement (response) without achieving remission. This combination is an indication that the doctors are making use of an effort to get more, this is good as well for treatment remission. Or, a good sign that the patient reports of adverse effects of this doctor is sensitive.

Very nice. Thanks you. Family docs (and even OB folk) seemed strangely partial to it (expressedly for lack of sexual side effects) as monotherapy, despite presence of comorbid anxiety for which, as you point out, we don’t have positive evidence.

If Wellbutrin is being increasingly prescribed, either on its own or as augmentation, perhaps physicians are preferring it in cases where they are treating chain-smoking clinical depressives who want or need to quit smoking. Just a thought.